Marcella Simone, Braile Mariantonia, Grimaldi Anna Maria, Soricelli Andrea, Smaldone Giovanni
IRCCS SYNLAB SDN, I-80146 Naples, Italy.
Oncol Lett. 2025 Feb 13;29(4):182. doi: 10.3892/ol.2025.14928. eCollection 2025 Apr.
Cancer participates in the immune response by releasing several factors, such as cytokines and chemokines, which can alter the ability of the immune system to identify and eradicate cancer. Notably, the role of thymic stromal lymphopoietin (TSLP) in breast cancer (BC) is currently controversial and unclear. The present study characterized the role of TSLP in BC and its interaction with peripheral blood mononuclear cells, focusing on the CD14CD16 monocyte population via the secretome released by BC cells. The UALCAN and Gene Expression Profiling Interactive Analysis tools were employed to define TSLP expression in BC, and its levels in different BC subtype cell lines were validated using reverse transcription-quantitative PCR and ELISA. In addition, TIMER 2.0 was used to determine the abundance of immune cell infiltration in BC. Subsequently, the effects of BC conditioned medium (CM) and TSLP were investigated on CD14CD16 monocytes via flow cytometry. A Cellular Reactive Oxygen Species (ROS) Assay Kit, Fluo-4 AM assay and ATPlite assay were used to explore the effects of TSLP on monocyte cellular metabolism. The results showed that a reduction in TSLP expression was associated with an unfavorable prognosis in BC. Furthermore, a higher expression of TSLP in CM from a non-tumoral cell line increased the percentage of CD14CD16 monocytes. Finally, it was revealed that TSLP decreased intracellular ATP levels, while increasing intracellular calcium levels and producing ROS in THP-1 cells. Therefore, TSLP may be considered a novel biomarker in the BC microenvironment, where it could regulate cellular metabolism through the expansion of CD14CD16 monocytes.
癌症通过释放多种因子(如细胞因子和趋化因子)参与免疫反应,这些因子可改变免疫系统识别和根除癌症的能力。值得注意的是,胸腺基质淋巴细胞生成素(TSLP)在乳腺癌(BC)中的作用目前存在争议且尚不清楚。本研究通过BC细胞释放的分泌组,重点研究了TSLP在BC中的作用及其与外周血单个核细胞的相互作用,特别是CD14CD16单核细胞群体。使用UALCAN和基因表达谱交互式分析工具来确定BC中TSLP的表达,并通过逆转录定量PCR和ELISA验证其在不同BC亚型细胞系中的水平。此外,使用TIMER 2.0来确定BC中免疫细胞浸润的丰度。随后,通过流式细胞术研究BC条件培养基(CM)和TSLP对CD14CD16单核细胞的影响。使用细胞活性氧(ROS)检测试剂盒、Fluo-4 AM检测和ATPlite检测来探索TSLP对单核细胞细胞代谢的影响。结果表明,TSLP表达降低与BC的不良预后相关。此外,非肿瘤细胞系CM中TSLP的高表达增加了CD14CD16单核细胞的百分比。最后,研究发现TSLP降低了细胞内ATP水平,同时增加了细胞内钙水平并在THP-1细胞中产生ROS。因此,TSLP可能被认为是BC微环境中的一种新型生物标志物,它可以通过CD14CD16单核细胞的扩增来调节细胞代谢。